Abstract: TH-PO0350
PLIN5 Overexpression Remodels Lipid Droplet-Mitochondria Contacts and Confers Mild Protection from Kidney Injury in Alport Syndrome
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Zevola, Mario, University of Miami Miller School of Medicine, Miami, Florida, United States
- Kim, Jin Ju, University of Miami Miller School of Medicine, Miami, Florida, United States
- Njeim, Rachel, University of Miami Miller School of Medicine, Miami, Florida, United States
- Insenga, Arianna, University of Miami Miller School of Medicine, Miami, Florida, United States
- Molina David, Judith T., University of Miami Miller School of Medicine, Miami, Florida, United States
- Khuu, Nicholas, University of Miami Miller School of Medicine, Miami, Florida, United States
- Fontanella, Antonio Miguel, University of Miami Miller School of Medicine, Miami, Florida, United States
- Saadat, Saeida, University of Miami Miller School of Medicine, Miami, Florida, United States
- Mitrofanova, Alla, University of Miami Miller School of Medicine, Miami, Florida, United States
- Merscher, Sandra, University of Miami Miller School of Medicine, Miami, Florida, United States
- Fornoni, Alessia, University of Miami Miller School of Medicine, Miami, Florida, United States
Background
Podocyte lipid accumulation and mitochondrial dysfunction contribute to kidney disease progression in Alport Syndrome (AS). Perilipin 5 (PLIN5) is a lipid droplet (LD)–associated protein that regulates triglyceride (TG) lipolysis and LD–mitochondria interactions, thereby influencing fatty acid (FA) handling and lipotoxic stress. We hypothesized that reduced PLIN5 expression in podocytes disrupts LD–mitochondria communication, leading to excessive TG breakdown, accumulation of free FAs and mitochondrial dysfunction, and that restoring PLIN5 levels might re-establish proper LD–mitochondria coupling and ameliorate these defects.
Methods
Immortalized Col4a3 KO (AS) and wild-type (WT) podocytes were generated from Col4a3-deficient and control mice. PLIN5 was overexpressed in AS podocytes by lentiviral infection, and LD–mitochondria contacts were visualized by transmission electron microscopy and quantified. FFA levels, TG lipolysis and apoptosis were measured by biochemical assays and cell-death analysis. In vivo, PLIN5 overexpression was induced in Col4a3 KO and WT mice using an adeno-associated virus (AAV PLIN5). Renal injury was evaluated by albumin-to-creatinine ratio (ACR), blood urea nitrogen (BUN), serum creatinine and histologic assessment of mesangial expansion.
Results
In AS podocytes, PLIN5 expression was reduced compared to WT podocytes(p<0.05). PLIN5 overexpression in AS podocytes in vitro restored LD mitochondria contact area when compared to AS control podocytes and was associated with reduced TG lipolysis, intracellular FFA content and apoptosis(p<0.05). In Col4a3 KO mice injected with AAV–PLIN5, renal injury showed a trend toward improvement, with lower albumin–to–creatinine ratio and BUN that did not reach statistical significance, whereas mesangial expansion was significantly reduced compared with AAV–WT–injected controls (p<0.05), while serum creatinine and body weight were largely unchanged.
Conclusion
PLIN5 overexpression enhances LD–mitochondria coupling and improves lipid handling in AS podocytes in vitro and partially ameliorates kidney injury in vivo. These data support the hypothesis that dysregulated podocyte lipid metabolism and impaired LD–mitochondria crosstalk contribute
to the progression of renal disease in AS and identify PLIN5-dependent LD remodeling as a potential therapeutic target in glomerular disease.
Funding
- NIDDK Support